inv(11)(q21;q23) in therapy related leukemias

Clinics and Pathology

Disease	Therapy-related acute leukemia and myelodysplastic syndromes (MDS).
Phenotype / cell stem origin	M2-ANLL, acute monocytic leukemia, MDS, T-ALL.
Etiology	Latency from twenty months to six years after chemotherapy.
Pathology	inv(11) positive cells were detectable six years prior to apparent leukemia in one case. MLL-MAML2 positive cells were detectable up to two years prior to apparent leukemia in another case. Whole genome expression profiles demonstrated differential expression of both typical MLL and NOTCH downstream genes.

Cytogenetics

	inv(11)(q21q23) G-banding.
	Detection of MLL rearranged cell by fluorescence in situ hybridization (FISH) with an MLL split signal probe.

Genes involved and Proteins

Gene Name	MAML2
Location	11q21
Dna / Rna	Spans 365 kb; 5 exons a major transcript of 7.5 kb.
Protein	1153 aa, 125 kDa; conserved N-terminal basic domain (aa 29-92) which binds to the ankyrin repeat domain of Notch receptors; two acidic domains (aa 263-360 and 1124-1153) and a C-terminal transcriptional activation domain.

Gene Name	MLL
Location	11q23
Dna / Rna	21 exons, spanning over 100 kb; 13-15 kb mRNA.
Protein	3969 amino acids; 431 KDa; contains two DNA binding motifs: a AT hook homologous to high mobility group proteins HMGI-(Y) and HMGI(C) that binds to the minor groove of DNA , and zinc fingers, a DNA methyl transferase motif, a bromodomain, and segments of homology with trithorax, in particular in the C-terminal SET domain.

Result of the chromosomal anomaly

Hybrid gene

Description	MLL-MAML2
Transcript	MLL-MAML2; exon 1-7 of MLL fused to exons 2-5 of MAML2.

Fusion Protein

Description	Hybrid transcript MLL/MAML2 contains the following domains: from MLL: AT-hook, DNA-Methyltransferase; from MAML2: Q rich domain, acidic domain.
Expression Localisation	In the nucleus.

External links

Other database	inv(11)(q21;q23) in therapy related leukemias	Mitelman database (CGAP - NCBI)

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity: you are welcome to submit a paper to our new Case Report section.

Bibliography

Secondary monocytic leukemia with rearrangement of the MLL gene occurring during the course of adult T-cell leukemia.

Obama K, Furukawa Y, Tara M, Niina K

International journal of hematology. 1998 ; 68 (3) : 323-326.

PMID 9846017

Inv(11)(q21q23) fuses MLL to the NOTCH co-activator mastermind-like 2 in secondary T cell acute lymphoblastic leukemia.

Metzler M, Zuna J, Stagee MS, Harder L, Meyer C, Flohr T, Meerpohl J, Fronkova E, Langer T, Harbott J, Trka J, Siebert R, Marschalek R, Niemeyer CM, Rascher W

Blood (ASH Annual Meeting Abstracts). 2006 ; 108.

Therapy-related acute myeloid leukemia 6 years after clonal detection of inv(11)(q21q23) and MLL gene rearrangement.

Takei N, Suzukawa K, Mukai HY, Itoh T, Okoshi Y, Yoda Y, Nagasawa T

International journal of hematology. 2006 ; 83 (3) : 247-251.

PMID 16720556

Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).

Nemoto N, Suzukawa K, Shimizu S, Shinagawa A, Takei N, Taki T, Hayashi Y, Kojima H, Kawakami Y, Nagasawa T

Genes, chromosomes & cancer. 2007 ; 46 (9) : 813-819.

PMID 17551948

Contributor(s)

Written	06-2007	Kazumi Suzukawa
		Department of Clinical and Experimental Hematology, Major of Advanced Medical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan

Citation

This paper should be referenced as such :

Suzukawa K . inv(11)(q21;q23) in therapy related leukemias. Atlas Genet Cytogenet Oncol Haematol. June 2007 . URL : http://AtlasGeneticsOncology.org/Genes/inv11q21q23ID1471.html

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indexed on : Wed Sep 24 21:06:01 2008

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